Understanding improved dissolution of indomethacin through the use of cohesive poorly water-soluble aluminium hydroxide: Effects of concentration and particle size distribution

Tay, T, Allahham, A, Morton, D and Stewart, P 2011, 'Understanding improved dissolution of indomethacin through the use of cohesive poorly water-soluble aluminium hydroxide: Effects of concentration and particle size distribution', Journal of Pharmaceutical Sciences, vol. 100, no. 10, pp. 4269-4280.


Document type: Journal Article
Collection: Journal Articles

Title Understanding improved dissolution of indomethacin through the use of cohesive poorly water-soluble aluminium hydroxide: Effects of concentration and particle size distribution
Author(s) Tay, T
Allahham, A
Morton, D
Stewart, P
Year 2011
Journal name Journal of Pharmaceutical Sciences
Volume number 100
Issue number 10
Start page 4269
End page 4280
Total pages 12
Publisher Elsevier
Abstract The objective of this study was to explore the effects of concentration and particle size distribution of an added poorly water-soluble inorganic salt, aluminium hydroxide, on the dissolution of a poorly water-soluble drug, indomethacin (IMC), from lactose interactive mixtures. Dissolution was studied using the United States Pharmacopeia paddle method in buffer pH 5.0 and the data most aptly fitted a bi-exponential dissolution model which represented dissolution occurring from dispersed and agglomerated particles. The dispersion of IMC mixtures was measured in dissolution media under non-sink conditions by laser diffraction. The dissolution of IMC increased as a function of the concentration of aluminium hydroxide (5-20%) added to the mixtures. Increasing the proportion of larger particles of the cohesive aluminium hydroxide increased the dissolution rate of IMC. The enhanced dissolution was attributed to increases in both the dissolution rate constant and initial concentration of dispersed particles. Mechanistically, the aluminium hydroxide was found to facilitate the detachment of IMC particles from the carrier surface, forming a complex interactive mixture that more readily deagglomerated than the cohesive drug agglomerates. The outcomes of this work would therefore allow more careful control and selection of the excipient specifications in producing solid dosage formulations with improved dissolution of poorly water-soluble drugs.
Subject Pharmaceutical Sciences
Keyword(s) Aluminium hydroxide
Deagglomeration
Dispersion
Dissolution
Excipients
Indomethacin interactive mixtures
Mathematical models
Oral drug delivery
Particle sizing
Poorly water-soluble drugs
DOI - identifier 10.1002/jps.22605
Copyright notice © 2011 Wiley-Liss and the American Pharmacists Association
ISSN 0022-3549
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